Background
Methods
Collected information
Assessments and definitions
Statistical analysis
Ethics
Results
Baseline patient characteristics
Disease
|
No. of patients
|
M/F
|
Median age
*
(y) (IQR, TR)
|
Median disease duration
*
(y) (IQR)
|
---|---|---|---|---|
AOSD
| 35 | 12/23 | 40.9 (22.4, 21.4-79.4) | 4.4 (7.4, 0.04-46.9) |
Gout
| 28 | 24/4 | 57.4 (11.5, 29.0-86.3) | 1.6 (8.5, 0.03-37.2) |
SJIA
| 27 | 17/10 | 7.3 (9.35, 2.1-29.1) | 1.4 (5.2, 0.11-24.1) |
CAPS
| 21 | 11/10 | 25.9 (22.5, 3.8-66.3) | 20.7 (25.3, 0.5-54.7) |
FMF
| 14 | 4/11 | 21.1 (33.7, 5.9-60.8) | 13.1 (19.5, 5.3-42.9) |
MKD
| 12 | 5/7 | 9.5 (14.9, 1.4-36.1) | 9.5 (15.6, 0.83-34.9). |
SAPHO
| 9 | 4/5 | 49.1 (18.8, 25.2-59.0) | 10.6 (14, 1.2-26.3) |
Schnitzler’s syndrome
| 7 | 5/2 | 55.3 (22.0, 49.9-76.2) | 7.4 (6.2, 3.5-13.7) |
Spondyloarthritis
| 5 | 4/1 | 44.1 (18.9, 31.2-72.5) | 10.3 (7.3, 5.1-13.4) |
Vasculitis
| 4 | 3/1 | 69.5 (18.6, 58.7-83.6) | 6.7 (6.1, 3.8-15.9) |
Chondrocalcinosis
| 4 | 1/3 | 67.9 (18.8, 46.8-83.6) | 3.7 (2.8, 0.5-10.4) |
GPP
| 3 | 2/1 | 55.5 (21.1, 44.3-72.4) | 17.1 (13.4, 8.5-35.5) |
Polychondritis
| 3 | 1/2 | 42.2 (27.5, 29.8-66.4) | 9.1 (10.9, 8.3-30.1) |
TRAPS
| 3 | 1/2 | 47.8 (29.5, 12.5-51.7) | 31.2 (19.1, 9.3-47.5) |
Anti–IL-1 treatments
Anakinra
Disease
|
No. of patients
|
Clinical response (available data)
|
Median treatment duration (days) (IQR)
|
Associated
*
treatment
|
CCS
|
DMARDs
|
Still treated
|
Associated treatment reduction
| ||
---|---|---|---|---|---|---|---|---|---|---|
None
|
Partial
|
Total
| ||||||||
AOSD
| 35 | 3 (8.6%) | 12 (34.3%) | 19 (54.3%) | 461 (1164) | 28/34 (82.4%) | 24/28 (85.7%) | 26/28 (92.9%) | 15/35 (42.9%) | 25/34 (73.5%) |
Gout
| 28 | 0 | 6 (21.4%) | 22 (78.6%) | 7 (96.5) | 20/27 (74.1%) | 7/20 (35%) | 0 | 3/24 (12.5%) | 22/24 (91.7%) |
sJIA
| 26 | 3 (11.5%) | 12 (46.2%) | 11 (42.3%) | 502 (1154) | 22/23 (95.7%) | 20/22 (90.1%) | 9/22 (40.9%) | 10/26 (38.5%) | 22/25 (88%) |
CAPS
| 21 | 0 | 6 (28.6%) | 15 (72.4%) | 1059 (1235) | 7/18 (38.9%) | 3/8 | 2/9 | 10/21 (47.6%) | 11/13 |
FMF
| 13 | 1 (7.6%) | 6 (46.2%) | 6 (46.2%) | 390 (814.5) | 10/12 (83.3%) | 4/12 (33.3%) | 2/12 (16.7%) | 7/13 (53.8) | 6/9 (66.7%) |
MKD
| 10 | 0 | 7 (70.0%) | 3 (30.0%) | 266 (448) | 3/4 | 1/4 | 0/4 | 3/10 | 3/3 |
SAPHO
| 9 | 4 (44.4%) | 4 (44.4%) | 1 (11.1%) | 86 (337) | 4/8 | 1/4 | 1/4 | 2/9 | 3/6 |
Schnitzler’s syndrome
| 7 | 1 (16.7%) | 0 | 5 (83.3%) | 479 (1227) | 4 (/5) | 2/4 | 1/4 | 4/7 | 5/6 |
Spondyloarthritis
| 5 | 4 | 1 | 0 | 30 (10–91) | 3/5 | 1/5 | 0/5 | 0/5 | 3/5 |
Vasculitis
| 4 | 0 | 2 | 1 | 424 (94–916) | 3/3 | 3/3 | 1/3 | 2/4 | 3/3 |
Chondro
calcinosis
| 4 | 1 | 2 | 1 | 52 (6–227) | 2/4 | 1/4 | 1/4 | 2/4 | 2/4 |
GPP
| 3 | 0 | 0 | 3 | 56 (6–129) | 2/3 | 1/3 | 0/3 | 1/3 | 2/3 |
Polychondritis
| 3 | 0 | 2 | 1 | 395 (110–1961) | 3/3 | 3/3 | 3/3 | 1/3 | 2/3 |
TRAPS
| 3 | 0 | 2 | 1 | 215 (29–225) | 3/3 | 3/3 | 0/3 | 2/3 | 2/3 |
NAPS12
| 2 | 0 | 2 | 0 | 797 | 2/2 | 0/2 | 0/2 | 0/2 | 0/2 |
Disease
|
No. withdrawals/treated patients
|
Inefficacy or loss of efficacy
|
Adverse event
|
Persistent remission
|
On-demand treatment
|
Patient request
|
Switch to canakinumab
|
---|---|---|---|---|---|---|---|
AOSD
| 20/35 | 14 | 3 | 1 | 0 | 2 | 2 |
Gout
| 18/28 | 0 | 0 | 17 | 1 | 0 | 0 |
SJIA
| 16/26 | 7 | 3 | 5 | 0 | 1 | 6 |
CAPS
| 11/21 | 1 | 1 | 1 | 0 | 8 | 3 |
MKD
| 7/10 | 2 | 2 | 0 | 0 | 3 | 4 |
FMF
| 6/13 | 1 | 3 | 0 | 1 | 1 | 3 |
SAPHO
| 7/9 | 5 | 2 | 0 | 0 | 0 | 0 |
Schnitzler’s syndrome
| 3/7 | 1 | 2 | 0 | 0 | 0 | 1 |
Spondylo arthritis
| 5/5 | 2 | 3 | 0 | 0 | 0 | 0 |
Vasculitis
| 2/4 | 2 | 0 | 0 | 0 | 0 | 2 |
Chondro calcinosis
| 2/4 | 1 | 0 | 1 | 0 | 0 | 0 |
TRAPS
| 1/3 | 1 | 0 | 0 | 0 | 0 | 0 |
GPP
| 2/3 | 1 | 0 | 1 | 0 | 0 | 0 |
Polychondritis
| 1/3 | 1 | 0 | 0 | 0 | 0 | 0 |
NAPS12
| 2/2 | 2 | 0 | 0 | 0 | 0 | 0 |
Canakinumab
Disease
|
Patient no.
|
First anti–IL-1
|
Dose and frequency
|
Clinical response
|
Treatment duration (d)
|
Associated treatment
|
CCS
|
DMARDs
|
Still treated
|
---|---|---|---|---|---|---|---|---|---|
AOSD
| 1 | No | 150 mg/4 wk | No | 148 | No | No | No | No |
AoSD
| 2 | No | 150 mg/8 wk | Total | 31 | Yes | Yes | No | Yes |
sJIA
| 3 | No | 4 mg/kg/4 wk | Partial | 61 | Yes | Yes | Yes | No |
sJIA
| 4 | No | 150 mg/8 wk | Total | 499 | UK | UK | UK | No |
sJIA
| 5 | No | 150 mg/4 wk | No | 31 | Yes | Yes | Yes | No |
sJIA
| 6 | No | 4 mg/kg/4 wk | Partial | 28 | Yes | Yes | No | No |
sJIA
| 7 | No | 3 mg/Kg/4 wk | No | 28 | Yes | Yes | No | No |
sJIA
| 8 | No | 4 mg/kg/4 wk | No | 28 | Yes | Yes | No | No |
sJIA
| 9 |
Yes
| 4 mg/kg/4 wk | Partial | 538 | Yes | Yes | Yes | No |
FMF
| 10 | No | 2 mg/kg/8 wk | Partial | 731 | Yes#
| No | No | Yes |
FMF
| 11 | No | 2 mg/kg/8 wk | Partial | 1151 | Yes#
| No | No | Yes |
FMF
| 12 | No | 2 mg/kg/8 wk | Total | 589 | Yes#
| No | No | Yes |
FMF
| 13 |
Yes
| 2 mg/Kg on demand | Total | 966 | Yes#
| No | No | Yes |
MKD
| 14 |
Yes
| 2 mg/kg/8 wk | Partial | 802 | Yes | Yes | No | Yes |
MKD
| 15 |
Yes
| 2-3* mg/kg/8 wk | Partial | 1112 | No | No | No | Yes |
MKD
| 16 | No | 3 mg/kg/8 wk | Total | 1101 | UK | UK | UK | Yes |
MKD
| 17 | No | 2 mg/kg/8 wk | Total | 957 | No | No | No | Yes |
MKD
| 18 | No | 7 mg/kg/8 wk | Partial | 558 | Yes** | No | No | Yes |
MKD
| 19 | No | 3.5 mg/kg/8 wk | Total | 163 | UK | UK | UK | Yes |
Vasculitis
| 20 | No | 150 mg/8 wk | Partial | 181 | Yes | Yes | No | No |
Vasculitis
| 21 | No | 150 mg/8 wk | UK | UK | UK | UK | UK | No |
Schnitzler’s syndrome
| 22 | No | 150 mg/8 wk | Partial | 385 | No | No | No | Yes |
TRAPS
| 23 | No | 2 mg/kg/4 wk | Total | 170 | Yes*** | No | No | Yes |
Erdheim Chester
| 24 | No | 2 mg/kg/8 wk | Partial | 679 | Yes | Yes | No | Yes |
Blau syndrome
| 25 | No | 150 mg/8 wk | Total | 390 | Yes | Yes | No | Yes |
Drug efficacy per disease
Tolerance of anti–IL-1 treatment
Anakinra
Adults
|
Children
| ||||
---|---|---|---|---|---|
Patient no.
|
Disease
|
SAE
|
Patient no.
|
Disease
|
SAE
|
1 | Gout | Pulmonary abscess | 1 | sJIA | MAS and EBV infection |
2 | AOSD | Pneumonia | 2 | sJIA | MAS and hepatitis |
3 | AOSD | VZV infection | 3 | sJIA | MAS, severe lipodystrophy and leishmaniasis* |
4 | AOSD | MAS and infection | 4 | sJIA | Death, toxidermia** |
5 | Schnitzler’s syndrome | Cancer, death | 5 | sJIA | Scarlet fever |
6 | MKD | Severe bronchitis | |||
7 | Vasculitis | Sinusitis | |||
8 | Polychondritis | Cutaneous abscess and osteitis | |||
9 | Pustular dermatosis | Septicemia | |||
10 | FMF | Quincke oedema | |||
11 | GPP | Severe cutaneous allergic reaction |
Canakinumab
Anakinra vs. canakinumab
Risk factors for AEs on anakinra
Any adverse event
|
Non cutaneous adverse event
| |||||||
---|---|---|---|---|---|---|---|---|
Patient variables
|
Univariate analysis
|
Multivariate analysis
|
Univariate analysis
|
Multivariate analysis
| ||||
OR (95% CI)
|
p
|
OR (95% CI)
|
p
|
OR (95% CI)
|
p
|
OR (95% CI)
|
p
| |
Paediatric vs. adult | 5.67 (2.37 to 13.60) |
0.0001
| 3.27 (1.16 to 9.21) |
0.03
| 1.83 (0.90 to 3.73) | 0.10 | - | n.s. |
Treatment duration | 2.12 (1.15 to 3.89) |
0.02
| - | n.s | 2.61 (1.34 to 5.13) |
0.005
| 3.37 (1.46 to 7.80) |
0.01
|
Background treatment:
| ||||||||
Methotrexate | 0.44 (0.21 to 0.95) |
0.03
| - | n.s. | 0.61 (0.26 to 1.41) | 0.25 | - | n.s. |
All DMARDs | 0.47 (0.23 to 0.98) |
0.04
| 0.27 (0.11 to 0.64) |
0.003
| 0.72 (0.33 to 1.59) | 0.42 | ||
Corticosteroids | 1.17 (0.57 to 2.38) | 0.68 | 0.82 (0.38 to 1.75) | 0.62 | ||||
NSAIDs | 1.38 (0.58 to 3.29) | 0.47 | 0.67 (0.26 to 1.74) | 0.41 | ||||
Disease:
| ||||||||
AOSD | 1.36 (0.72 to 2.57) | 0.35 | - | n.s. | 0.91 (0.46 to 1.79) | 0.78 | ||
sJIA | 6.53 (1.87 to 22.7) |
0.004
| - | n.s. | 1.42 (0.58 to 3.48) | 0.45 | ||
Gout | 0.06 (0.02 to 0.21) |
0.0001
| 0.05 (0.001 to 0.24) |
0.0002
| 0.07 (0.01 to 0.51) |
0.01
| - | n.s. |
CAPS | 1.37 (0.52 to 3.61) | 0.53 | - | n.s. | 1.97 (0.77 to 5.10) | 0.16 | - | n.s. |